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Updated: Jun 8, 2025
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
TP53 Mutation Status in Myelodysplastic Neoplasm and Acute Myeloid Leukemia: Impact of Reclassification Based on the
Hyun-Young Kim1, Saeam Shin2, Jong-Mi Lee3
1Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Background:
TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications.
Methods:
This study included patients aged ≥ 18 yrs who were diagnosed as having MDS (N=1,244) or AML (N=2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed.
Results:
TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF >50% for the 5th WHO classification and the presence of a complex karyotype for the ICC.
Conclusions:
Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.
Insights
TP53 mutations impact prognosis in myelodysplastic neoplasm (MDS) and AML. This study analyzed TP53 mutation characteristics in Korean patients, aiding diagnostic strategies under new classifications.
Area of Science:
- Hematology
- Oncology
- Molecular Genetics
Background:
- TP53 mutations are linked to poor prognosis in myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML).
- Updated classifications (5th WHO, ICC) recognize TP53-mutated MDS and AML as distinct entities.
- Understanding TP53 mutation characteristics is crucial for diagnosis and prognosis.
Purpose of the Study:
- To investigate the molecular genetic characteristics of TP53-mutated MDS and AML in a Korean cohort.
- To analyze diagnostic aspects based on the 5th WHO classification and International Consensus Classification (ICC).
- To identify key factors for applying TP53 mutation-related criteria in updated diagnostic guidelines.
Main Methods:
- Multicenter study including 1,244 MDS and 2,115 AML patients (≥18 years).
- Analysis of bone marrow examination, cytogenetics, and targeted next-generation sequencing for TP53 mutations.
- Evaluation of TP53 variant allele frequency (VAF) and correlation with karyotype and classification criteria.
Main Results:
- TP53 mutations occurred in 9.3% of MDS and 9.2% of AML patients.
- Missense mutations were most common, with specific hotspot codons identified.
- Complex karyotype was frequent (78.4%), and median TP53 VAF was 41.5%.
Conclusions:
- Elucidated molecular genetic features of TP53-mutated MDS and AML.
- Highlighted critical factors (VAF, complex karyotype) for applying TP53 criteria in updated WHO and ICC classifications.
- Aids in establishing diagnostic strategies for TP53-mutated hematologic malignancies.
